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An IFNg-dependent immune-endocrine circuit lowers blood glucose to potentiate the innate anti-viral immune response (Lung)

ABSTRACT: Viral infection makes us feel sick. The extent of these changes to our metabolism are relative to the severity of disease. Whether blood glucose levels are subject to infection-induced modulation is largely unknown. Here we show that strong, non-lethal infection restricts systemic glucose availability which promotes the antiviral IFN-I response. Following systemic viral infection of mice, we find that IFNγ produced by γδ T cells directly stimulates pancreatic β-cells to increase glucose-induced insulin release. Subsequently, hyperinsulinemia lessens endogenous glucose output by the liver. Glucose restriction enhances type-I interferon production by curtailing lactate-mediated inhibition of IRF3 and NF-κB signaling. Induced hyperglycemia constrained IFN-I production and increased mortality upon infection. Our findings identify glucose restriction as a physiological mechanism to bring the body into a heightened state of responsiveness to viral pathogens. This immune-endocrine circuit is disrupted in hyperglycemia, which explains why patients with metabolic disease are more susceptible to viral infection.

ORGANISM(S): Mus musculus

PROVIDER: GSE263600 | GEO | 2024/04/14

REPOSITORIES: GEO

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An IFNg-dependent immune-endocrine circuit lowers blood glucose to potentiate the innate anti-viral immune response

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